The main objective of this proposal is to investigate the involvement of the complement system in hypersensitivity pneumonitis. This study is a pilot investigation relating to a number of preliminary observations on the in vitro interactions of complement with extracts of organisms associated with the disease. These preliminary observations have suggested the complement can be consumed through the classical pathway, when mediated by immunoglobulin, or through the alternate pathway in the absence of detectable immunoglobulins. This proposal is designed to substantiate this observation and to answer certain pertinent questions about these observations. Hemolytic assays will be used to measure the consumption of early components of the classical and alternate complement consumption. Classical biochemical techniques will be used with emphasis on column chromatography, gel filtration and ion exchange. Particular emphasis will be placed on separating the complement consuming activity from the proteolytic activity associated with extracts of the thermophilic actinomyces. The agents will then be used to examine the effect on peripheral complement levels following inhalation challenge in an animal model.